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Identification of a macrocyclic compound targeting the lassa virus polymerase.
Aida-Ficken, Virginia; Kelly, Jamie A; Chatterjee, Payel; Jenks, M Harley; McMullan, Laura K; Albariño, César G; Montgomery, Joel M; Seley-Radtke, Katherine L; Spiropoulou, Christina F; Flint, Mike.
Afiliación
  • Aida-Ficken V; Viral Special Pathogens Branch, Division of High-Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA; Department of Pathobiology, College of Veterinary Medicine, Auburn University, Auburn, AL
  • Kelly JA; Viral Special Pathogens Branch, Division of High-Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA.
  • Chatterjee P; Viral Special Pathogens Branch, Division of High-Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA.
  • Jenks MH; Viral Special Pathogens Branch, Division of High-Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA.
  • McMullan LK; Viral Special Pathogens Branch, Division of High-Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA.
  • Albariño CG; Viral Special Pathogens Branch, Division of High-Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA.
  • Montgomery JM; Viral Special Pathogens Branch, Division of High-Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA.
  • Seley-Radtke KL; Department of Chemistry & Biochemistry, University of Maryland, Baltimore County, Baltimore, MD, USA.
  • Spiropoulou CF; Viral Special Pathogens Branch, Division of High-Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA.
  • Flint M; Viral Special Pathogens Branch, Division of High-Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA. Electronic address: vfa3@cdc.gov.
Antiviral Res ; 228: 105923, 2024 08.
Article en En | MEDLINE | ID: mdl-38844175
ABSTRACT
There are no approved vaccines or therapeutics for Lassa virus (LASV) infections. To identify compounds with anti-LASV activity, we conducted a cell-based screening campaign at biosafety level 4 and tested almost 60,000 compounds for activity against an infectious reporter LASV. Hits from this screen included several structurally related macrocycles. The most potent, Mac128, had a sub-micromolar EC50 against the reporter virus, inhibited wild-type clade IV LASV, and reduced viral titers by 4 orders of magnitude. Mechanistic studies suggested that Mac128 inhibited viral replication at the level of the polymerase.
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Texto completo: 1 Base de datos: MEDLINE Asunto principal: Antivirales / Replicación Viral / Compuestos Macrocíclicos / Virus Lassa Idioma: En Revista: Antiviral Res Año: 2024 Tipo del documento: Article

Texto completo: 1 Base de datos: MEDLINE Asunto principal: Antivirales / Replicación Viral / Compuestos Macrocíclicos / Virus Lassa Idioma: En Revista: Antiviral Res Año: 2024 Tipo del documento: Article